Estrogen Use Found to Cut Risk of Alzheimer’s

In the largest such study to date, federal researchers have found that estrogen replacement therapy among post-menopausal women decreases the risk of developing Alzheimer’s disease by more than 50%.

Experts said the new study--which included 472 women monitored for 16 years--is important because it is the first long-term analysis of estrogen’s effects on the devastating disease that affects more than 4 million Americans. Earlier studies had hinted at such a beneficial effect but were much smaller and covered periods of up to only a few months.

The finding, reported today in the journal Neurology, is the latest in a series of reports suggesting that estrogen replacement therapy has a broad range of dramatically beneficial effects. Several studies have shown that estrogen replacement therapy not only increases bone density and lowers cholesterol levels, but also decreases the risk of colon cancer, improves skin tone and even extends life span.

But research also has suggested the therapy may carry an increased risk of breast and uterine cancer, blood clots and gallstones in women with family histories of those diseases.

Although experts agreed that most post-menopausal women probably should be taking estrogen because there are so many beneficial effects, “there really are downsides to estrogen for a small population,” cautioned Dr. Claudia Kawas of the Johns Hopkins Bayview Medical Center in Baltimore, one of the co-leaders of the study. The decision to take the drug, she said, “really has to be between a woman and her doctor.”

Today’s estrogen results highlight estrogen’s emergence as the newest weapon in the growing arsenal of drugs that may delay or prevent Alzheimer’s. The findings follow on the heels of two other recent studies that found significant protective effects against Alzheimer’s from Vitamin E, the anti-Parkinson’s drug selegiline and the anti-inflammatory drug ibuprofen. Researchers are hurriedly designing clinical trials that will determine the benefits when two or three are taken together.

“We’re going to be giving people cocktails [of drugs],” said Kawas. “We’ll make a little dent in several parts of the disease pathway, and ultimately will have a major clinical effect.”

A statement from the Alzheimer’s Assn. noted that “this is a much-needed confirmation of earlier studies” that suggested estrogen might have a protective effect, but also echoed Kawas’ caution, urging women not to use estrogen “solely to protect against Alzheimer’s disease.”

Alzheimer’s is characterized by memory loss, disorientation, depression and a deterioration of bodily functions. It is ultimately fatal, causing about 100,000 deaths in the United States each year. Its cause is not known.

Researchers have suspected that lack of estrogen--the primary female sex hormone--might play a role in its onset, however. “The brain is a major target for estrogen, as important as the breast, bones or the cardiovascular system,” said neurologist C. Dominique Toran-Allerand of the Columbia College of Physicians & Surgeons.

Studies in animals and cultured cells show that lack of estrogen can have significant deleterious effects on nervous system structure and function, she said. “So it is not surprising that replacing estrogen in post-menopausal women would have beneficial effects,” she said.

In a study reported in November, Dr. Sanjay Asthana and his colleagues at the University of Washington Health Sciences Center found that giving estrogen to 12 elderly Alzheimer’s victims for two months tripled their memory ability and doubled their concentration. Other preliminary studies have found similar beneficial effects, but all such studies have been small and covered only short periods of therapy.

The new results cover more subjects and a much longer period of time. They are from the National Institute on Aging’s Baltimore Longitudinal Study on Aging, a 40-year study of more than 2,000 people that examines different aspects of aging. Every two years, people enrolled in the study return to Bayview for two and a half days of intensive medical study.

Kawas and Dr. E. Jeffrey Metter and his colleagues at the institute examined 472 women from the Baltimore study, 230 of whom had reported use of estrogen replacement therapy. Because of constraints in the study, the team lumped together women who had taken only estrogen with women who had taken estrogen combined with progesterone. The two hormones are frequently used in combination to reduce the risk of breast and uterine cancer.

“But we have no reason to believe that progesterone would block the estrogen effect,” Metter said.

During the 16-year follow-up period, the researchers found that only nine of the women taking estrogen developed Alzheimer’s, compared with 25 women in the group that did not take estrogen.

“This is strong evidence that estrogen plays a role in warding off the onset of this devastating disease,” Kawas said.

The team was also able to show that the protective effects of estrogen operated independently from those of ibuprofen, but the study was not large enough to determine if the protective effects of an estrogen/ibuprofen combination were greater than that of either drug taken alone.

“We need more studies,” Kawas said. “We need to find which components [of estrogen mixtures] are providing the benefit, which part of the molecules, and how they are doing it.”

The study may eventually have some implications for men as well. Males have the same estrogen receptors in their brain as females do, Toran-Allerand said, even though they do not have levels of circulating estrogens. Instead, testosterone is converted to estrogen in the brain by enzymes in brain tissue.

Men may undergo a long, slow decline in testosterone function, but they don’t have the sharp plunge in hormone levels that women face at menopause. “Men have a big advantage,” Toran-Allerand said. “That may be why the incidence of Alzheimer’s disease is higher among women.”

It needs to be determined, she added, whether men with Alzheimer’s have unusually low levels of testosterone and whether testosterone supplementation can stave off Alzheimer’s in them as well.

Several pharmaceutical companies are also trying to develop so-called designer estrogens that might benefit men as well as women. The drugs would retain the part of the estrogen molecule that provides beneficial effects while eliminating the parts that cause feminization in men or cancer in women.

(BEGIN TEXT OF INFOBOX / INFOGRAPHIC)

Estrogen’s Pros, Cons

A new study shows that estrogen replacement therapy can reduce the risk of Alzheimer’s disease by at least 50% among post-menopausal women. Other potential benefits of estrogen therapy, as well as some risks:

POSSIBLE BENEFITS

* Prevents osteoporosis.

* Decreases cholesterol levels and other risk factors for heart disease.

* Extends life span.

* Reduces risk of colon cancer.

* Makes skin smoother.

* Prevents vaginal dryness and thinning of walls.

* Provides relief from menopausal symptoms such as hot flashes.

* Prevents cataracts.

* Reduces symptoms of Alzheimer’s disease and delays onset.

****

POSSIBLE RISKS

(For women with family histories of these diseases.)

* May cause uterine cancer if used without progesterone.

* May cause blood clots.

* May cause gallstones in women at risk.

* May increase risk of breast cancer.